Abstract
Matrix Gla protein (MGP), a local inhibitor of tissue mineralization, is associated with vascular calcification. Depending on the carboxylation and phosphorylation status, MGP has active conformations, e.g., carboxylated MGP (cMGP) and phosphorylated MGP (pMGP), but also inactive conformations, e.g., uncarboxylated MGP (ucMGP) and dephosphorylated MGP (dpMGP). Our purpose was to assess the presence of all MGP conformations in healthy veins (HV) and varicose veins (VV), concurrently with the analysis of circulating total MGP (tMGP) before and after the surgical stripping of VV. We collected samples from the great saphenous vein, considered as control group, and tissue from VV, designated as VV group. Plasma levels of tMGP were significantly decreased after the surgical removal of the VV (before 59.5 ± 17.2 vs. after 38.1 ± 11.3, p < 0.001). By using immunohistochemistry staining, we identified local cMGP and pMGP in the control and VV groups, both without calcification, while ucMGP and dpMGP were absent. cMGP was observed in the nucleus and cytoplasm and pMGP in the nucleus of cells belonging to the tunica media, tunica intima and vasa vasorum. Therefore, the active conformations of MGP (cMGP and pMGP) are prevalent in HV and VV without calcification, affirming their anti-calcifying role in veins.
Highlights
To elucidate if Matrix Gla protein (MGP) has a local contribution as an anti-calcifying mediator at venous level, we decided to evaluate whether the active or inactive conformations are prevalent within the varicose veins (VV) and healthy veins (HV) and to assess the circulating total MGP (tMGP) levels
(black arrow); (B) phosphorylated MGP (pMGP) distribution in the vasa vasorum and adipocytes of the VV. This is the first study to identify the presence of carboxylated MGP (cMGP) and pMGP, as well as the absence of uncarboxylated MGP (ucMGP) and dephosphorylated MGP (dpMGP), in HV and VV without calcification
In VV with an abundance of local ucMGP in calcified VV, while cMGP was predominant in HV
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The varicose veins (VV) of the lower limb are superficial, dilated and twisted veins, tributaries to the saphenous or non-saphenous veins [3] This common condition with a complex and multifactorial etiology, including venous hypertension, extracellular matrix remodeling or venous reflux due to failure of the valves, is sometimes associated with calcification [4]. Cario-Toumaniantz et al [5] showed that local ucMGP is abundant in calcified veins and VV, cMGP is prevalent in healthy veins (HV), while increased MGP expression was associated with extracellular matrix (ECM). To elucidate if MGP has a local contribution as an anti-calcifying mediator at venous level, we decided to evaluate whether the active (cMGP and pMGP) or inactive (ucMGP and dpMGP) conformations are prevalent within the VV and HV and to assess the circulating tMGP levels. The objective of our pilot study was to investigate all MGP conformations in VV and HV as well as to assess their distribution within the venous wall by using immunohistochemistry staining
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